Patients frequently request removal of benign papular naevi for cosmetic or functional reasons. Shave excision plus electrocautery is probably the most widely used method of removal, but this method is said to result in retained hair or pigment if deeply pigmented or hairy naevi are treated. In a prospective study, 82 benign papular naevi of all types were treated by shave excision using hot-wire electrocautery for haemostasis. Details of the naevi were accurately recorded before treatment and reassessment of shave sites carried out at 6-8 months. At review, a scar was visible at only 63% (52/82) of shave sites and all of these were cosmetically acceptable. Only 27% (15/55) of the initially pigmented naevi retained pigment and only 24% (5/21) of the initially hairy naevi regrew hair. Shave excision and electrocautery of benign naevi, including hairy and deeply pigmented ones, produce excellent cosmetic results. The patient must be warned that there is a potential risk of a scar or pigment remaining after shave excision of any naevus and for hair regrowth after shave excision of hairy naevi.
intermittent cyclical etidronate therapy increased lumbar spine BMD over a 2-year period in an unselected group of men with osteoporotic vertebral fractures. This treatment warrants further evaluation in a randomized controlled trial.
SUMMARY. In Down's syndrome screening using biochemical markers, the marker concentrations are adjusted for the gestational age of the fetus, since they are known to change with gestational age. This adjustment is performed by referring to the population median of each marker for the appropriate gestational age group. The measurement of gestational age is subject to error, whatever method is used, and the population median used is actually the median of a mixture of distributions for different true gestational ages. We show how the proportions in this mixture can be estimated and how the true median corresponding to a given true gestational age can be estimated. For simplicity, we consider the case of using a single marker, namely maternal serum o-fetoprotein, and show that the usual estimation method has considerable bias. The effect of this mixture on the calculation of patient-specific risks is discussed and we show that detection rates can be improved by allowing for this error in the dating process. The overall detection rate is increased by about 10/0. The increase in detection rate is age-dependent and for some maternal ages the increase is of the order of 5%. The comparative effects of different methods for dating are discussed. Additional key phrases: a-fetoprotein; biochemical markers; gestational ageThe statistical procedure used when testing a fetus for risk of developing Down's syndrome in the second trimester relies on the reporting of a number of analyte concentrations as multiples of the median (MoMs). This procedure has become generally accepted because it is believed that by this method it is possible to remove the centreto-centre variation and the variation arising from the fact that the analytes measured vary with gestational age. I ,2 In an earlier paper, 3 we commented upon the problems associated with combining such MoM values; in particular we drew attention to the fact that when MoM values are combined from several sources, such as centres or gestational age groups, the result is a mixture distribution and not a Gaussian distribution as is usually assumed. This idea of mixtures led us to investigate the consequences to the screening procedure of errors in the dating process. In this paper we show that each group Correspondence: Dr B J Nix. 464of fetuses of a given estimated gestational age (EGA) is actually a mixture of patients with different true gestational ages (TGA). The magnitude of the difference between the estimated and true gestational ages, and hence the degree of mixing, depends on the accuracy of the dating process. Hence, for any group of a given EGA, the distribution of analyte concentrations is actually a mixture distribution with components from different TGA groups. We show that failure to take these errors into account can lead to substantial errors in the estimation of the median for each age group and hence to errors in the calculation of the patient-specific risks which are derived from the medians. The extent of the misclassification leading to the mixture varies ...
SUMMARY. When screening for Down's syndrome using biochemical markers, the measurements are adjusted for the gestational age of the fetus because the concentrations of the markers are known to change with gestational age. This adjustment is performed by referring each marker measurement to the population median for that marker for the appropriate estimated gestational age group. The measurement of gestational age is subject to error, whichever method is used, and so the population median used is usually the median of a mixture of distributions for different true gestational ages. Most screening programmes aim for a specific number of weeks and this produces a concentrated distribution of true gestational ages. This fact, combined with dating errors, leads to an asymmetric mixture for each gestational age group and hence to bias in the estimates of the medians. In a previous communication we have shown how the proportions in this mixture distribution can be estimated and how the true medians corresponding to a true gestational age can be estimated. The calculations presented were performed using a single marker, and the details of our method were restricted to this situation. This paper extends the method to the multimarker situation and, as expected, leads to a gain in the detection rate for a specified false positive rate. The true patient-specific risk estimates are again markedly different from the quoted nominal value obtained by ignoring the dating errors. The data set on which the method is illustrated uses two markers, although the technique generalises in an obvious way to more than two. Additional key phrases: alpha-fetoprotein; human chorionic gonadotrophinFor many years it has been recognized that analytes used in screening for Down's syndrome, such as maternal serum z-fetoprotein (MSAFP) and human chorionic gonadotrophin (HCG), vary with the estimated gestational age of the fetus.' While it has been recognized that gestation dating is not exact, and some have attempted to estimate the effect of this variability on certain risk factors.? until recently! no one has fully quantified the effect of dating errors. We have shown;' for a single analyte, how these dating errors affect the medians for different estimated gestational age groups, which in turn affect the calculations of the multiples of the median (MoMs) and patientCorrespondence Dr A B J Nix. specific risks. The methods we proposed enabled the true medians to be estimated by identifying the true age-dependent distributions. The calculations were illustrated by using MSAFP measurements taken from the database provided by the Royal Gwent Hospital screening programme for Down's syndrome. At this centre the target gestational age for screening was 16 weeks and the majority of women reported with an estimated gestational age of 16 or 17 weeks. The dating errors, combined with this concentration of estimated gestational ages, meant that many of those at, say, 15 weeks would in fact have a true gestational age of 16 weeks but have been misclassified, ...
Numerous papers have been written to show which combinations of Shewhart-type quality-control charts are optimal for detecting systematic shifts in the mean response of a process, increases in the random error of a process, and linear drift effects in the mean response across the assay batch. One paper by Westgard et al. (Clin Chem 1977;23:1857-67) especially seems to have attracted the attention of users. Here we derive detailed results that enable the characteristics of the various Shewhart-type control schemes, including the multirule scheme (Clin Chem 1981;27:493-501), to be calculated and show that a fundamental formula proposed by Westgard et al. in the earlier paper is in error, although their derived results are not seriously wrong. We also show that, from a practical point of view, a suitably chosen Cusum scheme is near optimal for all the types and combinations of errors discussed, thereby removing the selection problem for the user.
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